It is estimated that approximately 340,000 Americans and 100,000 Canadians are injection drug users (IDUs). Injection drug use can lead to overdose death, infectious disease spread, loss of social and economic functioning, and extensive engagement in criminal activity. For these reasons, interventions that may affect the natural history of injecton drug use, and in turn reduce these consequences, are of international interest. This study proposes to: determine the incidence of initiation into injection drug use among high-risk non-injection drug using youth and to elucidate individual, cultural, and environmental risk factors for initiation of injection; to evaluate the natural history of injection drug use from initiation to cessation or death, and to examine how specific environmental factors and interventions, such as prevention programs or addiction treatment interventions, can influence this natural history; to determine individual, cultural, and environmental barriers to the use of secondary prevention services, addiction treatment, and medical care; and to evaluate how trends in service use affect the incidence of HIV and associated risk behaviors as well as rates of mortality among a cohort of active IDUs. Vancouver is ideally suited to the proposed research questions for several reasons. First, the incidence of initiation into injection drug use among high-risk youth in our setting remains high. Second, the city is home to ongoing high rates of overdose mortality and HIV incidence among active IDUs. Second, British Columbia has a province-wide, centralized program of free access to highly active antiretroviral therapy (HAART), and a universal healthcare system that provides all medical care, including addiction treatment, free of charge. Understanding the mechanisms and interventions that affect the natural history of injection drug use, and the incidence of the consequences of injection drug use, are critical questions in North America. As such, this project will help inform prevention strategies and interventions throughout North America and elsewhere.